Recent evidence suggests that during aging there is widespread accumulation of aggregated insoluble proteins, even in the absence of pathological conditions. Pharmacological manipulation of protein aggregation might be helpful to unveil the involvement of protein aggregates during aging, as well as to develop novel strategies to delay aging. Here we investigated the effect of known protein aggregation inhibitors on the lifespan and health-span of Caenorhabditis elegans. For this purpose, we selected various structurally diverse anti-aggregation compounds and screened them in liquid and solid medium for their ability to alter the rate of aging in vivo. Our results show that treatment of C. elegans with diverse aggregation inhibitors significantly increases the animal lifespan and health-span. These findings indicate that protein misfolding and aggregation may play an important role in cellular dysfunction during aging, opening a novel approach to increase longevity and enhance the quality of life during aging.
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http://dx.doi.org/10.1016/j.bbrc.2016.10.143 | DOI Listing |
Background: With the approval of several anti-amyloid antibodies and a robust pipeline of new amyloid-based therapies, attention turns towards questions related to real-world clinical practice. Here we explore the impact of several biological pathways on the amyloid biomarker response of AD patients using a Quantitative Systems Pharmacology (QSP) approach with the ultimate objective to find measurable biomarkers for responder identification.
Method: Using a well-validated QSP biophysically realistic model of amyloid aggregation, we performed sensitivity analysis to identify key drivers of amyloid biomarkers both in a longitudinal observational context and after treatment with specific amyloid antibodies.
Alzheimers Dement
December 2024
Clinical Neurochemistry Laboratory Sahlgrenska University Hospital, Mölndal, Sweden.
Background: This research introduces a novel method for quantifying aggregated tau in body fluids, specifically cerebrospinal fluid (CSF), aiming to enhance the diagnosis and monitoring of neurodegenerative diseases, with a focus on Alzheimer's disease (AD).
Method: By combining tau protein amplification with a highly sensitive single-molecule array (Simoa) immunoassay using an anti-tau antibody CT19.1 in a homogenous manner, the approach enables precise measurements of tau aggregates in CSF.
Alzheimers Dement
December 2024
Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Background: The nuclear clearance and cytoplasmic aggregation of splicing repressor TAR DNA/RNA-binding protein-43 (TDP-43) occur in approximately 50% of Alzheimer's disease (AD) cases and about 45% of frontotemporal dementia (FTD). However, it is not clear how early such mechanism occurs in AD and FTD as there is no method of detecting TDP-43 dysregulation in living individuals. Since the loss of nuclear TDP-43 leads to cryptic exon inclusion, we propose that cryptic exon-encoded peptides may be detected in patient biofluids as biomarkers of TDP-43 loss of function.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Rheinland Pfalz, Germany.
Background: Parkinson's disease (PD) is a debilitating condition that affects millions of people worldwide, yet there are currently no reliable biomarkers for its diagnosis. Alpha-synuclein aggregation is a well-known hallmark of PD pathology, but the behavior and kinetics of these aggregates are poorly understood. To address this gap in knowledge, this study utilized several approaches to evaluate the potential of alpha-synuclein aggregates as potential biomarker for PD.
View Article and Find Full Text PDFBackground: The importance of detecting amyloid β (Aβ) in the early stages of Alzheimer's disease has markedly increased following the approval of Lecanemab, a disease-modifying drug. MRI is a non-invasive and less expensive rather than amyloid PET as gold standard for Aβ biomarker, but its clinical ability to detect Aβ has not been demonstrated. MRI phase information reflects paramagnetic substance including iron associated with Aβ aggregation.
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